HIV: disease control is given by lymph node cells – 05/19/2023 – Health

The defense cells present in the lymph nodes responsible for identifying the HIV virus in the body are able to induce an immune attack and prevent the proliferation of the virus in some people who are able to control the infection.

This mechanism is mediated by the expression of specific genes in CD8+ cells, also called cytotoxic, and involved in the identification of other parts of the body infected with the virus and the death of these cells.

In individuals who carry this gene, HIV control is carried out naturally for years, without the need for antiretroviral therapies, such as those used by patients with suppressed disease.

The mechanism involved in this immune response is unprecedented and was described in an article published this Friday (19) in the specialized journal Science Immunology, of the Science group.

The research has the participation of scientists from the Howard Hughes Medical Institute, the Ragon Institute, linked to Massachusetts General Hospital, and MIT (Massachusetts Institute of Technology, in Portuguese), all in the United States, and the Institute of Molecular Virology and Cellular of the Friedrich-Alexander University Erlangen-Nuremberg, in Germany.

Lymph nodes are areas of our body associated with the production of defense cells (known as lymphocytes) and which act in the detection and destruction of infected cells or cells with replication errors (as in tumor cells).

To assess the role of CD8+ cytotoxic cells in controlling HIV, the researchers analyzed samples of blood and lymph node cells from 19 patients called “spontaneous controllers” of HIV, 17 patients using antiretroviral therapy and seven people who are not carriers of the virus as a control group.

The research observed that in the spontaneous controllers there was an elevated expression of the CXCR5 gene in the CD8+ lymphatic cells that were “trained” to recognize the HIV-specific antigen (part of the virus against which the defense cells will attack).

This mechanism was already known. What the authors identified as unprecedented, however, was that these lymph cells “call” others to the germinal centers within the lymph nodes, thereby producing more attack cells—increasing, shall we say, the fleet of soldiers.

As cells expressing this gene were found in greater numbers in lymph nodes, along with other substances associated with the cell death process —known as cytotoxins–, the scientists imagined that the mechanism of re-stimulation, that is, more substances induce the production of new defense cells, occurred in these centers.

Differently from the patients being treated with the anti-HIV cocktail, the individuals who were able to control the disease had a high concentration of cytotoxins of the perforin and granzyme B type, associated with the action of cell death. These high concentrations indicate that the immune system was more able to identify, attack and destroy cells containing the virus, thus suppressing the action of the pathogen.

The so-called spontaneous controllers manage to maintain a rate of viremia (virus replication) below 2,000 copies per milliliter over 23 years.

For David Collins, a researcher at the Ragon Institute, at MIT and a professor at Harvard University and the first author of the study, it is still not possible to know whether these 19 individuals had innate gene expression – that is, they carried the mutation that stimulates the detection mechanism. and destruction of HIV in the organism – or if it was a control mechanism activated with the virus infection itself. “Since this mechanism has not been observed in patients using antiretroviral cocktails, future research will now determine whether this mechanism of lymph node cytotoxic cells may suggest a new therapeutic target for HIV control,” he told the Sheet.

According to him, the search for an anti-HIV vaccine is still a different type of approach, precisely because they seek to induce the production of neutralizing antibodies, which immediately block the replication of the virus in cells. “So far, this type of immune response has proven difficult to achieve and, even more so, with long-lasting protection and in sufficient quantity to control the disease. The cellular immune response of memory, such as this mechanism of spontaneous controllers, can be more easily induced and easier to direct, including against regions of the virus that are conserved between the different strains”, he says.

Research on therapies with antibodies or with stimulation of the immune system to combat the HIV virus are not new, but advances in the area are difficult, mainly due to the virus attack mechanism of hijacking the cells of the immune system to deceive it. Recently, a study showed that the antibody isolated from a patient with HIV was able to prevent infection in other individuals. Other research already indicates drugs currently used against cancer capable of expelling HIV from cells.

“We still need to better discover the exact location where this cellular mechanism of action against HIV began. Although our research has observed a high concentration of CD8+ cells in the lymph nodes, we know that they got there due to the high concentration of cytotoxins in these glands, thus activating other cells and preventing the proliferation of the virus. Preventing the entry of the virus into the cells in the first moment will be an important step for antiretroviral therapies”, he said.